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February 23, 2006

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Worms on front line of in study of space radiation study

A round trip to Mars could expose travellers to more than one-quarter the LD50 dose which means that one person in eight could die from radiation poisoning while the rest would be very sick.

The United States, and perhaps other countries, are planning a manned mission to Mars. Unfortunately, it's not known if humans can survive the 35-60 days' trip across 100-million kilometres of space to the rocky red planet.

Nor do we know what effects radiation will have on the travellers. We don't even know how much radiation they will be exposed to.

The Brookhaven National Laboratory in New York used its particle accelerator to attempt to simulate the radiation exposure of a round trip to Mars. The results showed an expected exposure of approximately 130,000 millirem - more than 370 times the annual average dose for North Americans (350 millirem). Scary stuff for the people going to Mars.

It gets worse. According to the University of California Davis' environmental health and safety website, the human LD50 is about 500,000 millirem. LD50 means a dose lethal enough to kill 50 per cent of the people exposed. So a round trip to Mars could expose the travellers to more than one-quarter the LD50 dose, which means that one person in eight could die from radiation poisoning while the rest would probably be very sick. This does not even take into account unpredictable solar flares which could increase the dose several fold.

The Brookhaven results may or may not be true. Little is known about the effects of long exposure to space radiation either aboard the International Space Station (ISS) - where there has been continual habitation for a few years - or for long-duration spaceflights such as the planned Mars mission. While manned spacecraft have been equipped with excellent radiation detection devices, they don't measure the harm that space radiation does to people.

What we need is a good system to collect data on the biological effects of radiation in space. That's where Worms in Space comes in - a set of projects involving SFU researchers that will hopefully lead to the development of radiation countermeasures enabling long-duration manned spaceflight and continual habitation aboard the ISS.

What are these worms? They are tiny nematodes called Caenorhabditis elegans. An adult is about 1 millimetre long - about as long as a grain of salt is wide. C. elegans has many advantages as a model system for studying the effects of radiation in space. One advantage is its small size. A C. elegans experiment doesn't need much room. This is important because it's expensive to launch weight into orbit and spacecraft, even the ISS, are very cramped. In addition, C. elegans has a generation time of just a few days; a two-week lifespan in which a single hermaphrodite produces about 300 offspring; a limited number of cells (less than 1,000); and it's easy to maintain in a laboratory. These advantages mean that experimental procedures can be short, flexible and cost effective. The worms can be kept in little bags so that the astronauts can just inject liquid food into the bags every few weeks.

Another advantage is that C. elegans is the simplest multi-cellular organism with a completely known genomic DNA sequence. Like humans, C. elegans has about 20,000 genes. About 4,500 of these genes are effectively doing the same jobs in worms as in humans. These similar genes include a large set whose job is to repair DNA damage. Not only does C. elegans have a similar number of genes to us, they have a lot of effectively the same genes and similar DNA repair systems, making C. elegans an excellent model for learning about potential biological damage to humans in the space environment.

C. elegans has already been to space on several missions. These include the 1993 and 1996 flights that carried experiments for Greg Nelson of the Jet Propulsion Laboratory (JPL); the 2003 Columbia flight, which crashed in Texas and carried experiments for Nate Szewczyk of the University of Pittsburg and Catharine Conley of NASA's Ames laboratory; and the 2004 First International C. elegans experiment (ICE-first) on the Delta mission in which Ann Rose, an SFU alumna, headed the Canadian Space Agency(CSA)-funded part of the four-country collaboration (Canada, France, Japan and the U.S.).

Believe it or not, live worms were recovered from the disaster of the Columbia. They survived an impact 2,295 times the force of Earth's gravity. "This is a very exciting result," said Catharine Conley of NASA (Astrobiology Article 1921). "It's the first demonstration that animals can survive a re-entry event similar to what would be experienced inside a meteorite. It shows directly that even complex small creatures originating on one planet could survive landing on another without the protection of a spacecraft."

The two JPL experiments and ICE-first used a C. elegans mutagen testing system developed in SFU professor David Baillie's NSERC-funded SFU laboratory by research associate Raja Rosenbluth and grad student Bob Johnsen, now a research associate. Called the eT1-system (named before the movie ET came out), the system can capture mutations in C. elegans' genome for analysis on the ground after a completed spaceflight.

Like us, C. elegans has two sets of chromosomes, so even if there is a mutant gene on one chromosome the normally functioning gene on the other is usually sufficient to perform that gene's function. The offspring of a worm with a mutant gene will get either the mutant or the normal gene. Because the normal gene does an important job while the mutant doesn't, over the generations worms with the normal gene will out-compete mutant worms and the mutation is eventually lost. This loss is not good if you want to analyse space radiation-induced genetic damage. The eT1 system maintains mutations so they won't be lost.

While the first worms-in-space experiments were for short-time (about one generation) exposure to space radiation during the JPL flight, the ICE-first experiment was for a little longer - 11 days in space. These short experiments yielded only a few mutations, not much above the number of spontaneous mutations we would expect on Earth.

This is likely because satellites in low Earth orbit, including the ISS, are protected by the Earth's magnetosphere. Trips to the Moon or Mars will last a lot longer and will not be protected by the magnetosphere. Nobody knows what biological effects these long trips will have on humans.

Here at SFU, we have a CSA grant to look into this problem. We will use the eT1 system to get an accurate assessment of the biological effects of long exposure to radiation on the ISS and from this we'll develop a biological accumulating dosimeter for longer trips.

Two of our research questions: How do biological systems respond to fluctuating dosages of different types of radiation in space? Do DNA repair systems work differently in space than on Earth? We will look at multi-generational effects (which can't be done with humans) by placing C. elegans on the ISS for several months. Our current plan is to fly the worms to the ISS in 2007-08. We are also having discussions with TRIUMF, located at UBC, to expose eT1-system worms to radiation in its particle accelerator, simulating the ISS environment.

Once we have radiation-exposed worms back at SFU we'll use newly developed Nimblegen DNA-array chip technology to analyse the worms. These chips contain bits of DNA from C. elegans' 20,000 genes, so by comparing the exposed worms with the chips we'll be able to rapidly identify any mutations.
















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